The SWITCH method, published in Cell in 2015, introduces a simple process for controlling a wide variety of chemical reactions during tissue processing of large animal and human samples. The method ensures uniformity of preservation and immunolabeling by synchronizing chemical reactions throughout the entire sample. There are 2 basic steps to the method: SWITCH-OFF, when chemicals and buffers are allowed to diffuse freely throughout the tissue, and chemical reactions are suppressed; and SWITCH-ON, when the buffer environment is rapidly changed to a condition allowing chemical reactivity. Tissue architecture, native biomolecules, and antigenicity are highly preserved in this method, allowing for multiple rounds (>20) of labeling.