In general, you set up the indexes during table creation. In this phase you should already have a good indication of how your data will be queried, and which fields will be used most as query criteria. During performance tuning, it is generally recommended to have the obvious indexes in place.

Is it good to have multiple indexes?

More indexes = more work on any write actions (insert/update/delete), so pick what you need and what you'll see a solid performance gain from. Think about not just the grouping order but also what's being referenced in your SELECT and WHERE clauses.

Are indexes necessary?

Indexes are used to quickly locate data without having to search every row in a database table every time a database table is accessed. Indexes can be created using one or more columns of a database table, providing the basis for both rapid random lookups and efficient access of ordered records.