The first was in '08/'09 - shortly after the iPhone. Some companies (Google, Samsung) saw where the industry was going, made the appropriate decisions and are now profiting handsomely. In hindsight, that was the right time for RIM to acquire QNX and start on BB10, which might have done very well had it come out in 2011. With decent hardware, a solid OS, their own style and riding on BBM (big at that time), they might have staked a sustainable 10-15% chunk of the market.
The second chance was '10/'11, around the time of Nokia's Burning Platform Memo. This is when RIM started on BB10, but as we see now, it was already too late. Had they bet heavily on Android and on their strengths (security, gov & enterprise sales), they might be doing pretty-well today.
I hope the Waterloo area survives this well.