This review covers important laboratory serological investigations specific to entities routinely encountered by orbitologists. The technique, parameters measured, and clinical importance of each of these laboratory tests are discussed in detail. Due to the extensive nature of the topic, the review has been split into 2 parts. Part I covers thyroid eye disease, IgG4-related disease, and myasthenia gravis. In part II of the review, sarcoidosis, vasculitis, Sjögren syndrome, and giant cell arteritis will be discussed.