The oxidation of sulfide minerals in waste rock has the potential to generate low-quality drainage that can present a significant challenge to mine owners, regulators, and other stakeholders. Challenges involved in managing waste rock include the large volume of waste rock produced and the difficulty in predicting the quality and quantity of leach water due to the chemical and physical heterogeneities in the waste rock, and the highly non-linear coupling of geochemical and physical processes. Many important studies have been conducted over the past decade, particularly at the field scale, that have investigated the geochemical, hydrological, microbiological, and gas and heat transport aspects of waste-rock. These studies show that although the parameters and processes that influence AMD generation and solute release are fundamentally similar between different waste-rock piles, major differences in the dominant mechanisms of water, gas and heat transport result from differences in the physical and mineralogical properties of the rock piles, and the climatic conditions, including the amount of precipitation and prevailing temperatures. Accurate prediction of the leach water quality from waste-rock requires a detailed characterization of the properties of the rock piles and the coupling of processes specific to the particular conditions. This paper provides a review of the physical and mineralogical characteristics of waste-rock piles, followed by a discussion of the principal processes related to sulfide oxidation and solute loading, and concluding with a discussion on acid mine drainage prediction and prevention techniques.