1. To undertake some journey or task. The team is setting off on an expedition into the darkest reaches of the jungle. Ten years ago, we set off on one of the most ambitious projects in history.

2. To issue forth some longwinded speech, story, tirade, etc. My uncle set off on another one of his cockamamie conspiracy theories. The senator set off on a diatribe about the danger of repealing the bill.

3. To instruct, cause, or compel someone to undertake some journey or task. In this usage, a noun or pronoun is used between "set" and "off." Losing my job set me off on a journey to rediscover what I truly wanted out of life. I'm setting the intern off on a tougher assignment to put what she has learned to the test.

4. To cause someone to issue forth some longwinded speech, story, tirade, etc. In this usage, a noun or pronoun is used between "set" and "off." Don't mention the new tax law if you don't want to set my father off on another rant! The song on the radio set my grandmother off on a story about her time in the dancehalls of the 1940s.