Mechanisms underlying the modulating effects of yogic cognitive-behavioral practices (eg, meditation, yoga asanas, pranayama breathing, caloric restriction) on human physiology can be classified into 4 transduction pathways: humoral factors, nervous system activity, cell trafficking, and bioelectromagnetism. Here we give examples of these transduction pathways and how, through them, yogic practices might optimize health, delay aging, and ameliorate chronic illness and stress from disability. We also recognize that most studies of these mechanisms remain embedded in a reductionist paradigm, investigating small numbers of elements of only 1 or 2 pathways. Moreover, often, subjects are not long-term practitioners, but recently trained. The models generated from such data are, in turn, often limited, top-down, without the explanatory power to describe beneficial effects of long-term practice or to provide foundations for comparing one practice to another. More flexible and useful models require a systems-biology approach to gathering and analysis of data.