Kada moju sestru boli glava, ona pije mnogo vode.

Serbian very often uses the verb boleti for physical pain. With this verb, the structure is different from English:

• glava = the thing that hurts
• moju sestru = the person who feels the pain

So the literal structure is closer to the head hurts my sister.

That is why Serbian says moju sestru boli glava rather than copying the English structure my sister has a headache.
You can also say moja sestra ima glavobolju, and that is perfectly understandable, but boli je glava / moju sestru boli glava is very common and natural.

Because with boleti, the person who experiences the pain is usually in the accusative.

So in:

Kada moju sestru boli glava...

• moju sestru = accusative
• it means my sister as the person affected by the pain

This is different from English, where my sister would be the subject. In Serbian, with boleti, the painful body part or condition is treated as the grammatical subject instead.

Because glava is the grammatical subject of boli.

In other words:

• glava = nominative singular
• boli = 3rd person singular, agreeing with glava

So the grammar is literally:

• glava boli moju sestru = the head hurts my sister

If the subject were plural, the verb would also be plural. For example:

• Oči je bole. = Her eyes hurt.

So boli is singular here because glava is singular.

Because moju has to agree with sestru.

The noun sestra here is:

• feminine
• singular
• accusative

So the possessive adjective moja changes to the matching form moju:

• nominative: moja sestra
• accusative: moju sestru

This kind of agreement is very important in Serbian: adjectives and possessives usually match the noun in gender, number, and case.

They mean the same thing here: when.

• kada is the full form
• kad is the shorter form, very common in everyday speech

So both of these are fine:

• Kada moju sestru boli glava, ona pije mnogo vode.
• Kad moju sestru boli glava, ona pije mnogo vode.

In casual Serbian, kad is often more common.

Yes, Serbian often drops subject pronouns when they are already clear from the verb form or context.

So this sentence can also be:

Kada moju sestru boli glava, pije mnogo vode.

That is perfectly natural.

Including ona adds a bit of emphasis or clarity, something like:

• she drinks a lot of water
• as for her, she drinks a lot of water

So ona is not wrong at all, but it is not strictly necessary.

Because mnogo normally requires the genitive.

With a mass noun like voda, that gives:

• nominative: voda
• genitive: vode

So:

• mnogo vode = a lot of water

Compare:

• mnogo knjiga = many books
• mnogo vremena = a lot of time

So vode is genitive here because it follows mnogo.

Because the sentence describes a habitual or general situation:

• whenever this happens, she drinks a lot of water

In Serbian, the present tense is commonly used for this kind of repeated action:

• Kada ... boli ... , ona pije ...

This does not necessarily mean it is happening right now. It means something like:

• When my sister gets a headache, she drinks a lot of water
• Whenever my sister has a headache, she drinks a lot of water

Also, pije is from the imperfective verb piti, which fits repeated or ongoing actions well.

You could, but it changes the feel.

• pije = imperfective, neutral for habitual or repeated action
• popije = perfective, often suggests a completed action, like drinks up or finishes drinking

So:

• ona pije mnogo vode = she drinks a lot of water
• ona popije mnogo vode = she drinks a lot of water up / she ends up drinking a lot of water

In a general statement like this, pije is the more neutral and expected choice.

No. Serbian word order is fairly flexible.

The given sentence is natural:

Kada moju sestru boli glava, ona pije mnogo vode.

But other versions are also possible, for example:

• Kada je boli glava, ona pije mnogo vode.
• Kad je boli glava, pije mnogo vode.

The version with je is especially common in everyday speech if it is already clear whose headache you are talking about.

You could also move words around for emphasis, but not every order sounds equally natural. For example, Glava boli moju sestru is grammatically possible, but in normal conversation it sounds less natural than Moju sestru boli glava or Boli je glava.

You would usually say:

Kada je boli glava, ona pije mnogo vode.

Here je means her and is the accusative clitic pronoun.

A very common shorter version is:

Kad je boli glava, pije mnogo vode.

A useful pattern to remember is:

• Boli me glava. = My head hurts / I have a headache.
• Boli te glava. = Your head hurts.
• Boli je glava. = Her head hurts.
• Boli ga glava. = His head hurts.

So this sentence fits a very common Serbian pattern.