Abstract Loneliness is reported by the majority of people with schizophrenia (∼80%), yet the cognitive and neural mechanisms underlying loneliness in this population are incompletely understood. Similar to the general population, loneliness in schizophrenia is associated with cognitive biases toward mistrusting others, as well as structural barriers to social activity. In addition, some evidence suggests that predisposing genetic and environmental factors, as well as some of the neural changes and the poor cardiometabolic health linked with the illness, are associated with loneliness in schizophrenia. However, much evidence supports a transdiagnostic model of the causes and consequences of loneliness, with similar factors playing a role in loneliness in schizophrenia and the general population. Currently there are no validated treatments targeting loneliness associated with schizophrenia, although interventions focusing on cognitive bias modification, positive psychology, mindfulness, or interpersonal synchrony have shown promise. Taken together, the current state of the field suggests that future research on schizophrenia should include measurements of social isolation and loneliness. Overall, there is a need for novel intervention approaches that can interrupt the cycle of mutually reinforcing neurocognitive biases and environmental conditions linked with loneliness in schizophrenia and other populations.