The use of the patented device/method/whatever, whether or not it is sold, is the infringement. Unwitting infringers are not subject to very harsh penalties, if any (unlike ignorance of the law, ignorance of a patent is a mitigating factor, b/c people are not required to research the patent archives for everything they do or make). Knowing infringers can be hit with the hammer of holy justice.

Example: patents on custom protein structures.

Note that pure research, i.e., at universities, is usually considered a defense b/c it is in the public interest to encourage actual research, but it is a defense that must be proven in court. However, research with any sort of commercial motive will usually not avoid infringement liability.

The reason that the "hundreds" of companies can get away with it is b/c it isn't worth the cost to the patent holder to pursue them in court -- damages would be minimal, and the chance that a defendant could find something that would overturn the patent (i.e., prior art) is too high a risk if there are at least some companies willing to pay for a license.