Persons who are deaf-blind represent a heterogeneous, low-incidence population of children and adults who, at some point in life, regardless of the presence of additional disabilities, may benefit from formal orientation and mobility (O&M) instruction. Current national policies, such as the No Child Left Behind Act, which emphasize that instructional practices must be validated through the use of scientific measurement using randomized clinical trials, present specific problems for O&M professionals who serve students who are deaf-blind. Heterogeneity within the population, diversity of settings, geographic spread, cost, random sampling, and ethical concerns present immediate challenges in conducting experimental group designs with persons who are deaf-blind. The Council for Exceptional Children's Division of Research and the National Center for Special Education Research have recognized that the alignment and systematic analysis of single-subject research can be used to evaluate the efficacy of practice. This type of research allows for the tailoring of intervention strategies to meet the unique needs of participants and may be implemented in an experimental fashion without relying on traditional parametric analysis. In the field of visual impairments, single-subject research has been used to measure the impact of teaching over the years. Parker et al. (2007) began an initial examination of single-subject methodology with participants who had dual sensory impairments; however, at this point, there has been no comprehensive review of single-subject research with participants who are deaf-blind specifically in O&M interventions. This article presents a study which sought to answer the following research questions: (1) What types of single-subject research were conducted with participants who are deaf-blind from 1965 to 2007 in the area of increasing O&M skills?; and (2) What types of interventions and practices were shown to be effective in building participants' competence in the areas of O&M?