This paper is an introduction to a special issue celebrating the 125^th anniversary of William James' Principles of Psychology. The special issue demonstrates the continued relevance and insight offered by James. It reviews the articles in this issue and delineates three main themes: (1) he recognition of the inherent relationality of psychological phenomena, (2) a science of psychology ought to include biology and sociocultural phenomena (e.g. language); and (3) human consciousness is addressed as the flow of experience from the perspective one living it. It discusses each theme and briefly touches on how they continue to be developed in James' later work, which also provides innovative new directions for psychologists. Undergirding each of these contributions is James' admonition that psychological research is especially difficulty due to the complexity of psychological phenomena. As such, this paper also discusses challenges to doing psychological research that James raises and his ideas that can inform future endeavors.