Grayscale lithography is a widely known but underutilized microfabrication technique for creating three-dimensional (3-D) microstructures in photoresist. One of the hurdles for its widespread use is that developing the grayscale photolithography masks can be time-consuming and costly since it often requires an iterative process, especially for complex geometries. We discuss the use of PROLITH, a lithography simulation tool, to predict 3-D photoresist profiles from grayscale mask designs. Several examples of optical microsystems and microelectromechanical systems where PROLITH was used to validate the mask design prior to implementation in the microfabrication process are presented. In all examples, PROLITH was able to accurately and quantitatively predict resist profiles, which reduced both design time and the number of trial photomasks, effectively reducing the cost of component fabrication.