Cognitive-behavioural therapy (CBT) is rightly considered a first-line psychological treatment for a plethora of psychological disorders due to its extensive research base. Evidence for schema therapy (ST) as a first-line treatment is strongest where personality disorders are concerned. With other high-occurrence disorders, once known as ‘axis 1 disorders’ (e.g. depression, anxiety disorders), evidence is now emerging for ST as a second-line treatment in its own right. From a schema therapy point of view, in focusing treatment on presenting ‘axis 1’ problems, patterns of avoidance and rigidity characteristic of underlying personality disorder pathology often remain unaddressed and can drive treatment non-response. In this chapter, we outline a ST approach to mood and anxiety disorders where ST may be considered as a second-line treatment option in those cases where there is (a) an inadequate response to first-line treatment (e.g. CBT) and/or (b) where significant symptoms of personality disorder, or traits thereof, are assessed to be maintaining the severity and/or chronicity of illness, including the engagement with and response to any treatment.