Fast heavy-ion collisions with molecules that constitute a liquid are fundamental to the field of radiation chemistry and its application to biology. However, although collision-induced physical and chemical processes in liquids have been extensively studied, the initial stages of such processes remain not fully understood because of their complex behaviors. Accordingly, our group has studied the initial reactions occurring in the vicinity of fast ion trajectories in liquids by mass spectrometric analysis of the secondary ions ejected from microdroplet surfaces upon fast heavy-ion impacts. In this topical review, we present our recent experimental advances in secondary-ion mass spectrometry using microdroplets of water, alcohols, and amino acid solutions. Our findings demonstrate the complex physicochemical behaviors of positive and negative product ions and highlight the role of secondary electrons in the mechanisms of biomolecular damage triggered by fast heavy ions.