The conventional 2-dimensional (2D) cell culture is an invaluable tool in, amongst others, cell biology and experimental pharmacology. However, cells cultured in 2D, on the top of stiff plastic plates lose their phenotypical characteristics and fail in recreating the physiological environment found in vivo. This is a fundamental requirement when the goal of the study is to get a rigorous predictive response of human drug action and safety. Recent approaches in the field of renal cell biology are focused on the generation of 3D cell culture models due to the more bona fide features that they exhibit and the fact that they are more closely related to the observed physiological conditions, and better predict in vivo drug handling. In this review, we describe the currently available 3D in vitro models of the kidney, and some future directions for studying renal drug handling, disease modeling and kidney regeneration. (C) 2016 Elsevier B.V. All rights reserved.