The aim of this study was to investigate what psychosocial predictors, life-style factors and health behaviors in early adulthood are of importance for self-ratings of health after the age of 45. Like-sexed adult twins born 1926-1950 (n = 16,080) from the Swedish Twin Registry that participated in a questionnaire in 1973 and in a telephone interview conducted between 1998 and 2002 were included. Exposure data was collected in 1973 and information on self-rated health and covariates was collected at the second contact 25 years later. Logistic regression using Generalized Estimating Equations was used to evaluate the associations. Conditional logistic regression was used to control for familial and genetic effects in the sample. Pain, lack of exercise, smoking, obesity, unemployment, perceived stress and personality are associated with future poor self-rated health, after controlling for age, sex, illness, education and socio-economic status. Familial and genetic effects influence the associations between recurrent headache, exercise, obesity, and poor self-rated health. Overall, these findings provide support for long-term effects of health behavior and psychosocial risk factors on poor self-ratings of health, beyond the influence of obvious health consequences such as disorders or illnesses. Genetic and familial factors are of importance only for some of these associations.