Regulatory T (T reg) cells suppress effector T (T eff) cells and prevent immune-mediated rejection of cancer. Much less appreciated are mechanisms by which T eff cells antagonize T reg cells. Herein, we consider how complex reciprocal interactions between T eff and T reg cells shape their population dynamics within tumors. Under states of tolerance, including during tumor escape, suppressed T eff cells support T reg cell populations through antigen-dependent provision of interleukin (IL)-2. During immune activation, T eff cells can lose this supportive capacity and directly antagonize T reg cell populations to neutralize their immunosuppressive function. While this latter state is rarely achieved spontaneously within tumors, we propose that therapeutic induction of immune activation has the potential to stably disrupt immunosuppressive population states resulting in durable cancer regression.