Macrophages play diverse roles in episodic T cell-mediated inflammatory diseases such as multiple sclerosis and rheumatoid arthritis, function as accessory cells for T cell activation, as pro-inflammatory cells, as effector cells which mediate tissue damage, and as anti-inflammatory cells which promote wound healing. In addition to the many roles of T cell-derived cytokines in differentially modulating these diverse macrophage activities, research over the last few years has demonstrated that contact-dependent signaling which occurs during T cell-macrophage adhesion is a critical triggering event in the activation of macrophage function. Substantial research emphasis has been placed on CD40 as a mediator of contact dependent signaling. However, other membrane-anchored receptor:ligand pairs may also contribute to the stimulation of macrophage function. This is a brief review of the rapidly expanding, but still incomplete, knowledge of how T cells, through both contact-dependent and cytokine signals, regulate macrophage function during inflammatory disease.