In the past four years the e-science group at the Academic Medical Center of the University of Amsterdam, NL, has researched how to make e-infrastructures more accessible to biomedical researchers. Experiments with various types of tools and interfaces have pointed out in the direction of "science gateways", a strategy that has been adopted by many. The development of science gateways (SGs), however, is far from straightforward. There are many technological and functional options, which tend to change along time. We are currently designing and implementing the fourth generation of SG, which follows a strong data-oriented approach. It is based on the generic platform of the WS-Pgrade/gUse portal adopted in the SCI-BUS project. In this talk we look back at the previous generations, present the main features of the current one, and discuss our experiences.