The gradual loss of quality in stored platelets as measured collectively with various metabolic, functional, and morphologic in vitro assays is known as the platelet storage lesion. With the advent of pathogen reduction technologies and improved testing that can greatly reduce the risk for bacterial contamination, the platelet storage lesion is emerging as the main challenge to increasing the shelf life of platelet concentrates. This article discusses the contribution of platelet production methods to the storage lesion, long-established and newly developed methods used to determine platelet quality, and the significance for clinical transfusion outcome. Highlighted are the novel technologies applied to platelet storage including platelet additive solutions and pathogen inactivation.