1. Missing or wrong indexes
The most common cause by a wide margin. Look at the actual execution plans for your slowest queries before guessing.
2. Queries that cannot use the index you have
Wrapping a column in a function, or a parameter type that does not match the column type, quietly disables the index. The plan will show a scan where you expected a seek.
3. Statistics that no longer reflect the data
After a large import, the optimiser may still be planning against yesterday's distribution. Update statistics and re-test before changing anything else.
4. Blocking, not slowness
A long-running write transaction can make every reader look slow. Check wait statistics before concluding the query itself is the problem.
Hardware is the last resort, not the first. We regularly recover an order of magnitude from indexing and query changes alone.