Angiogenesis is essential for progressive solid tumor growth and thus constitutes a very promising therapeutic target. Recent developments in understanding of the molecular mechanisms involved in tumor blood vessel formation provides a rational basis for anti-angiogenic drug development, especially of more selective and effective agents. However, for the very same reason, it is time to think more critically about some of the potential pitfalls and difficulties associated with this treatment strategy and of research needed to define realistic expectations in this area.