The roles played by physics in the study of the life sciences have taken many forms over the past 100 years. Here we analyze how physics can be brought to bear on the contemporary study of morphogenesis, where new tissue-scale forms arise out of simpler, more homogenous, initial structures. We characterize how morphogenesis has been studied through reductionist approaches and discuss their limitations. We suggest that an alternative way of approaching morphogenesis that begins with a consideration of the whole may (...) also serve as a fruitful mode of scientific inquiry. Through historical analysis of concepts relevant for contemporary systems biology, we illustrate how physical thinking oriented toward the biological whole (“holistic biophysical thinking”) was exemplified in the biological theories presented earlier by D’Arcy Thompson (1860–1948) and Pere Alberch (1954–1998). We contrast the use of physics to develop the conceptual foundations of holistically oriented systems biology with the more prevalent contemporary use of physics that focuses on technological development and quantification, embedded within reductionist strategies. As an in-depth contemporary case study, we describe how in our research we have used holistic biophysical thinking to develop biological theories of vertebrate morphogenesis that account for and extend beyond genetic, molecular, and cellular processes. We propose a theory of skin development where _both_ molecular _and_ morphological patterns are orchestrated by emergent physical processes at the supracellular scale. We further posit that holistic biophysical thinking at the supracellular scale may advance theories of diseases such as cancer. (shrink)