Effects of fluctuations of the imaging medium in and out of the focal plane (misfocus) are analyzed for laser photothermal imaging materials. Static and dynamic misfocus conditions degrade image quality by producing fluctuations in the imaged spot sizes. A theoretical model is developed for Gaussian profile laser pulses, and for uniform (top-hat) profile pulses delivered by a laser diode. Conditions which maximize the depth of focus are determined. The depth of focus can be made arbitrarily large by wasting laser energy. The maximum depth of focus for limited laser energy is found to be slightly above the fluence needed for imaging with maximum efficiency. Experimental results are presented for four different imaging media. One simple medium with a thin metal film on a clear polyester substrate, agrees almost perfectly with the theoretical model and therefore behaves “ideally”. More complicated media with other substrates and other surface layers, are shown to deviate from the theoretical model due to nonlocal behavior. Nonlocal behavior means laser energy incident on one region affects nearby regions. It is shown that purposely designing nonlocal behavior into imaging media can improve the depth of focus, in some cases by factors of two or three.