The nature of inpatient pediatrics is changing. Over the past decade, several factors have converged to influence the kinds of children currently being hospitalized. There has been a shift in the relative proportion of otherwise healthy children with acute illnesses being hospitalized to children with increasing medical complexity. This article focuses on hospitalist care of medically complex children and provides an overview on (1) the challenges in defining this population, (2) the unique issues surrounding their inpatient care (using a family-centered care approach that includes coordinated care, minimizing secondary complications, nutritional needs, functional limitations, transdisciplinary collaboration, and primary care issues), (3) technology devices commonly found, and (4) a proposal for a research agenda regarding medically complex children.