3D cell culture technologies have revolutionized our understanding of cellular behavior, both in culture and in vivo, but adoption by cell-based screening groups has been slow owing to problems of consistency, scale and cost. The evolving field of high content screening technologies will, however, require a rethinking of 3D cell culture adoption to ensure the next generation of cells provide relevant in vivo-like data. Three current technologies are presented in this review: membranes, sponges/gels and microcarriers. A short history of these technologies and unique research applications are discussed. Also, the technologies are evaluated for usefulness in modern automated cell-based screening equipment.