Microneedles (μNDs) have emerged as promising minimally invasive drug delivery systems, offering advantages such as painless administration and enhanced drug permeability. Among various μNDs technologies, responsive μNDs have attracted growing attention for their ability to react to physiological or external stimuli, allowing precise and on-demand drug release for both localized and systemic therapies. This review explores the recent advancements in responsive μNDs triggered by various endogenous and exogenous signals that correspond to specific targeted diseases and/or sites of application. Additionally, the review highlights the challenges associated with scalability, biocompatibility, and regulatory approval of responsive μNDs and provides insights into future directions for clinical translation. By consolidating the latest developments, this review aims to support the design and optimization of next-generation smart drug delivery systems.