Since being proposed as a unique subtype of late-life depression (LLD), the vascular depression hypothesis has received considerable research attention. Although this effort has generated considerable empirical support for the validity of the subtype, fundamental questions remain including how the illness is defined, whether cerebrovascular disease and executive dysfunction (ED) define two separate entities or one underlying subtype, and whether ED is responsible for poor response to antidepressant treatment. In this guest editorial, we explore these and other issues (i.e., the role of personality and social support, psychosocial treatments targeting cognitive abilities frequently impaired in LLD) using a number of important papers that are either directly or indirectly related to the vascular depression hypothesis. In so doing we highlight a range of critical problems facing the vascular depression hypothesis and the effort to establish the illness as a unique diagnostic entity in late-life.