Tissue processing is the technique by which fixed tissues are made suitable for embedding within a supportive medium such as paraffin, and consists of three sequential steps: dehydration, clearing, and infiltration. In most clinical and research settings, tissue processing is accomplished using an automated tissue processor, with or without microwave-assistance. To ensure high-quality results, processing protocols should be tailored to tissue size and composition by modifying variables such as reagents used and the timing of the various steps. Herein, we provide an overview of tissue processing theory and outline a basic tissue processing method for use with a conventional automated fluid transfer/enclosed processor. The principles described will assist readers in optimizing tissue processing for their own projects.