Assuming you aren't a Canadian citizen, the usual way is to apply for several companies who are willing to sponsor a H-1B visa and get an offer from one of them. Until a few years ago the number of applicants used to be way over the H-1B visa cap, so you had to go thru a lottery even if your application was OK. This was the number one reason I never even applied.
http://www.workpermit.com/us/us_h1b.htm
But recently the number of applicants has sharply decreased and is below the cap, so if you get the offer and pass all the requirements (have a college degree, etc) you should be able to get it.
One problem with H-1B is that if you lose or quit your job you have to get another job within 30 days. Personally I'd avoid early-stage startups because of that rule: I wouldn't want to be in a position to find a job that quickly.
Another possible problem is that your spouse can get a visa but cannot work (until you both get a green card, which might take a long time).
You should check out the websites of companies you'd like to work for and see if they do the H-1B thing. Also, check the list of top visa sponsors:
http://www.myvisajobs.com/Reports/Top-Visa-Sponsor-2011.aspx
I hope this helps.