The ability of T helper (T H) precursor cells to differentiate into T effector populations confers the adaptive immune system with a means to protect the host from microbes and react to “foreign” antigenic tissues. T-cell immunoglobulin and mucin domain (TIM) proteins have recently been shown to be novel and critical regulators of T cell subset-driven dependent immune responsiveness. A dichotomy is emerging as to how Tim-3–and Tim-2–related signals respectively impact T H 1 and T H 2 responses. By comparison, the influence of the Tim-1 pathway seems to be broader and is probably not restricted to a specific type of T helper response. Beyond the mere control of the T H 1/T H 2 balance, Tim proteins are likely to target other regulatory components of the T cell response. Likewise, it is tempting to speculate that Tim proteins might also modulate the function of other T helper cell subsets such as T H 3, T R 1 and T H 17 cells, among others.