While you play a song, notes will scroll along columns, towards the receptors at the end. When a note lines up with the receptors, press the corresponding button for that column.
There are also "hold notes" or "long notes" - For these notes you must press and hold the key for the column until the tail of the note reaches the receptor, when you must release the key.
You are scored on your accuracy as you play, which is displayed as a percentage.
The more accurately you timed your key press, the more points you get for each note.
For example in the SC scoring system, here's how points work:
Multiple scoring systems are available in Interlude, but the "official" one is SC.
You can read more about alternative score systems on the Rulesets page.