Mass spectrometry offers a unique lens for viewing biology, revealing molecular signatures that bridge chemistry and life. This talk traces my journey – from a technician in a Pfizer mass spectrometry lab to a biologically focused perspective on biological systems examined through MS. I will trace how the field’s priorities have evolved: from leveraging MS in small-molecule drug discovery and target classification to probing the dynamics of protein machineries and intact membrane assemblies. A central thread is the shift from overexpression-based preparation toward direct extraction from endogenous tissues and native membranes, enabling analyses that more faithfully reflect physiological conditions. I will map the progression through key technical and conceptual milestones, highlight the challenges and strategies for preserving native states, and discuss how these advances are increasingly accelerating translation toward clinical insight. In closing, I’ll outline emerging trends, the remaining hurdles, and the potential impact of MS-enabled biology on medicine.