Background: Cognitive impairment is an important target for novel therapies in schizophrenia, but measuring cognitive effects in schizophrenia trials raises practical and theoretical challenges. The MATRICS programme produced a consensus cognitive battery which is now in use in clinical trials in schizophrenia; however other cognitive assessments may be equally suitable. Methods: We review advantages and disadvantages of one such alternative, the computerized CANTAB schizophrenia battery, using MATRICS criteria including psychometric properties, relationship to functional outcome, sensitivity to pharmaceutical agents, and practicality. Following CNTRICS recommendations we also consider the utility of CANTAB in translational research. Results: CANTAB has been used in more than 70 peer-reviewed publications in psychotic disorders. The tests' neural bases have been mapped through patient, lesion and neuroimaging studies. The nonverbal nature of the CANTAB aids use in multinational trials and the tests are also available in directly translational forms for rodents and non-human primates. More work is required regarding the psychometric properties of CANTAB tests, especially in patient populations, and on the relationship of each test to functional outcomes. Computerized cognitive assessment may help improve the statistical power of cognitive trials by reducing measurement error and between-site variability, minimising practice effects, and decreasing patient attrition through increased tolerability. Discussion: Effective cognitive assessment in schizophrenia trials may be a major barrier to the development of new treatments for cognitive dysfunction. The CANTAB and MATRICS batteries assess the same cognitive domains but differ in their ease of use, psychometric validation, and translational use.