Previous research has found that very few, if any, psychological or physiological processes are universally beneficial. Instead, positive phenomena tend to follow a non-monotonic or inverted U-shaped trajectory where their typically positive effects eventually turn negative. This review investigates mindfulness-related processes for signs of non-monotonicity. A number of mindfulness-related processes-including, mindful attention (observing awareness, interoception), mindfulness qualities, mindful emotion regulation (prefrontal control, decentering, exposure, acceptance), and meditation practice-show signs of non-monotonicity, boundary conditions, or negative effects under certain conditions. A research agenda that investigates the possibility of mindfulness as non-monotonic may be able to provide an explanatory framework for the mix of positive, null, and negative effects that could maximize the efficacy of mindfulness-based interventions.