Research that explores youth transitions, health, bereavement and well-being is rare. Rarer still is research that does this on the basis of long-term, longitudinal, qualitative research with socio-economically disadvantaged young people. This paper draws upon biographical interviews undertaken with 186 young adults in some of England’s poorest neighbourhoods (in Teesside, North East England) to examine how experiences of health, well-being and bereavement interact with processes of youth transition and social exclusion. Depression was the most widespread health problem, arising from the multiple pressures and hardships encountered in contexts of severe socio-economic deprivation. Unpredictable ‘critical moments’ (e.g. of bereavement) were common and had unpredictable consequences for youth transitions. It is argued that research of this sort, particularly with a close, qualitative and biographical focus on ‘critical moments’, has value for research - about youth, health and well-being - that seeks to better understand how spatially concentrated, class-based inequalities are lived by young people and play out in their lives.