Objective: The aim was to determine if suicide note themes might inform suicide prevention strategies. Method: The themes of 42 suicide notes from the Northern Ireland Suicide Study (major psychological autopsy study) were examined. Results: The commonest themes were “apology/shame” (74%), “love for those left behind” (60%), “life too much to bear” (48%), “instructions regarding practical affairs post-mortem” (36%), “hopelessness/nothing to live for” (21%) and “advice for those left behind” (21%). Notes of suicides with major unipolar depression were more likely than notes of suicides without major unipolar depression to contain the themes “instructions regarding practical affairs post-mortem” (67% versus 19%, p = 0.005) and “hopelessness/nothing to live for” (40% versus 11%, p = 0.049). Notes of suicides with a previous history of deliberate self-harm were less likely than notes of suicides without a history of deliberate self-harm to contain the theme “apology/shame” (58% versus 87%, p = 0.04). Notes of elderly suicides were more likely than non-elderly notes to contain the theme “burden to others” (40% versus 3%, p = 0.03). Conclusions: The fact that three quarters of suicide notes contained the theme “apology/shame” suggests that the deceased may have welcomed alternative solutions for their predicaments. Scrutiny of suicide note themes in the light of previous research findings suggests that cognitive therapy techniques, especially problem solving, may have an important role to play in suicide prevention and that potential major unipolar depressive (possibly less impulsive) suicides, in particular, may provide fertile ground for therapeutic intervention (physical and psychological). Ideally all primary care doctors and mental health professionals working with (potentially) suicidal people should be familiar with basic cognitive therapy techniques, especially problem solving skills training.