It all depends on if your looking for a work at home "job" or a work at home "business."
Yes, if it's a job and they want you to pay upfront for whatever reason then most likely it's a scam. Try Apline Access or West, they are jobs you can do at home but you go through the hiring process like any other job you would in the outside world.
Now, as for the "business"-most home-based business do require a start-up cost or an overhead fee which covers marketing, materials and getting you set up for your business. When you have a home-based business you are your own boss and so you need to treat it as a new business (just the same as if you were opening up a new bakery for instance).
Good luck on your search and let me know if I can help in anyway.
T. Staten