Pharmaceutical science has moved away from focusing exclusively on the impact of medications on physiological parameters to a focus that includes the subject’s quality of life (QoL). To date, QoL assessment has relied exclusively on global summaries that ask subjects to recall, summarize, and evaluate their subjective QoL. New science-based methods using handheld technology to gather QoL data can lead to more valid, reliable, and timely QoL data. Many of the components of QoL, from subjective well-being to objective functioning, derive from an interest in understanding a subject’s daily and momentary experiences. Rather than relying on broad summaries of experience, a ‘bottoms-up’ approach to QoL assessment directly measures subjects’ momentary QoL in real-time, in the real-world. Until recently, researchers did not have an efficient way to collect valid momentary QoL data from subjects in their natural environment. Recent methodological advances in the science of patient experience, termed Ecological Momentary Assessment (EMA), make it possible to collect real-time QoL data from subjects using electronic patient experience diaries. This ‘bottoms-up’ approach using EMA methods extends existing QoL measures by providing a unique perspective on the extent to which subjects’ evaluations of various moments in their lives reflect QoL changes over time. Recent empirical evidence suggests that this ‘bottoms-up’ approach may enhance the sensitivity of QoL assessment in clinical trials. The new perspective EMA provides on momentary patient experience represents a promising methodological advancement in the study of QoL. In combination with standard written assessments of QoL, EMA data can provide a new perspective on the relationship between medication effects and QoL.