B7-H1, B7-DC, B7-H2, B7-H3, and B7-H4, all new additions to the B7 family, here termed "the new B7s," are emerging as important tools in directing immune function; each with unique, yet often overlapping functions. Clearly, each B7 molecule has developed its own indispensable niche in the immune system. The expression of both stimulatory and inhibitory B7 molecules seems to play an essential role in regulating the immune response to transformed cells through a variety of mechanisms. As specific niches of B7 family members continue to be dissected, their diagnostic and therapeutic potential becomes ever more apparent. In this review, we will discuss the role of the new B7s in activation and inhibition of antitumor immune responses, their prospects in diagnostics, and also potential and developing immunotherapy protocols.