We review the emergence of a diverse collection of modern Internet-scale programming approaches, collectively known as Web 2.0, and compare these to the goals of cyberinfrastructure and e-Science. e-Science has had success following the Enterprise development model, which emphasizes sophisticated XML formats, WSDL and SOAP-based Web Services, complex server-side programming tools and models, and qualities of service such as security, reliability, and addressing. Unfortunately, these approaches have limits on deployment and sustainability, as the standards and implementations are difficult to adopt and require developers and support staff with a high degree of specialized expertise. In contrast, Web 2.0 applications have demonstrated that simple approaches such as (mostly) stateless HTTP-based services operating on URLs, simple XML network message formats, and easy to use, high level network programming interfaces can be combined to make very powerful applications. Moreover, these network applications have the very important advantage of enabling “do it yourself” Web application development, which favors general programming knowledge over expertise in specific tools. We may conservatively forecast that the Web 2.0 approach will supplement existing cyberinfrastructure to enable broader outreach. Potentially, however, this approach may transform e-Science endeavors, enabling domain scientists to participate more directly as codevelopers of cyberinfrastructure rather than serving merely as customers.