The last few decades of psychosis research have focused on the first episode. Studying the illness at onset offers a better understanding of its social and biological risk factors, and outcome correlates, without the confounding effects of chronicity on brain or social functioning. Significant efforts have been devoted to the identification of predictors of both illness onset and subsequent clinical and functional outcomes using different approaches. Among these, neuroimaging has provided important findings on brain neuromorphological differences between individuals with psychosis who have different outcomes. This is the main focus of this commentary. It is important to note that the neuromorphological differences reported in the literature between subgroups of individuals with different outcomes have not been of clinical utility so far. Rather, these findings have highlighted the presence of high heterogeneity in the brain biology that underlies psychosis. Mindful of this challenge, researchers have been experimenting with new analytical approaches, such as those that bypass the need to compare groups defined by a priori clinical labels. Our biggest challenge in the future will be to identify measures which could be used, alone or in combination, for a more precise stratification in clinical trials of new compounds or more personalized interventions.