Induction therapy with biological agents was introduced the in the 1970s and the rationale, concepts and approach have remained almost unchanged for 30 years. However, the novel biological agents being developed for induction therapy are being, designed for chronic rather than short-term therapy with several objectives: reduce dependence on toxic and nephrotoxic agents, improve outcome and ultimately facilitate the emergence of tolerance. The biological agents include efalizumab, a humanized anti-CD11a (anti-LFA1), antiCD 154, anti-CD40, a number of agents targeting IL- 15 and its receptor, and costimulation blockade with humanized antibodies to CD80/CD86 and the fusion receptor protein LEA29Y, a second generation CTLA(4)Ig. The past decade has witnessed an unprecedented number of small molecules/oral drugs that have been developed and approved for renal transplantation-, the next decade, however, may witness the emergence of a new class of biological induction agents that may displace some of the currently used drugs.