Non-invasive brain stimulation (NIBS) is a complex and multifaceted approach to modulating brain activity and holds the potential for broad accessibility. This work discusses the mechanisms of the four distinct approaches to modulating brain activity non-invasively: electrical currents, magnetic fields, light, and ultrasound. We examine the dual stochastic and deterministic nature of brain activity and its implications for NIBS, highlighting the challenges posed by inter-individual variability, nebulous dose-response relationships, potential biases and neuroanatomical heterogeneity. Looking forward, we propose five areas of opportunity for future research: closed-loop stimulation, consistent stimulation of the intended target region, reducing bias, multimodal approaches, and strategies to address low sample sizes.