Omega-3 (ω3) fatty acids are associated with a variety of health benefits from normal neurologic development and vision, to heart disease, arthritis and cancer. The ω3 fatty acid docosahexaenoic acid in particular accumulates in biological membranes and there may serve either structural or substrate functions. Proteins resident in or associated with membranes are likely to be influenced by changes in their lipid environment. The mechanisms through which ω3 fatty acids exert their influence over proteins are not always clear, and may include direct interactions that induce conformational change, formation of membrane lipid microdomains of unique composition; modulation of eicosanoid production; participation in oxidation; and alteration of gene expression. Much of the complexity of this area stems from the often divergent effects that ω3 fatty acids have on different cell types in different states of activation. Here I present a sampling of proteins involved in various functions including adhesion, immunologic recognition, and signal transduction; the emphasis is on cells and processes of the immune system. Included are effects of free fatty acids and of fatty acyl chains esterified into phospholipids, and phenomena that appear unique to one or more ω3 fatty acids or that are common to several different fatty acid classes. Understanding basic mechanisms of ω3 fatty acid action, for example, on structure and function of membrane proteins will assist us in using these dietary components more effectively for human health.