This study was done to examine actor and partner effect of self-esteem and family stress on depression of middle-aged married couples. Methods: Participants were 133 couples aged 40-60 years, who lived in Seoul, Incheon, or Gyeonggi provinces. All measures were self-administered. Data were analyzed using SPSS 18.0 and AMOS 18.0 program. Results: Husband and wife``s self-esteem had an actor effect (wife β=-.45, p<.001; husband β=-.35, p<.001 respectively) on their depression. Wife``s family stress had an actor effect (β=.27, p=.006) on her depression and a partner effect (β=.31, p=.002) on her husband``s depression. Meanwhile, it also had an indirect effect on her depression through self-esteem (β=-.28, p<.001). Husband``s family stress did not have an actor effect or a partner effect on his depression, but it had an indirect effect on his depression through self-esteem (β=-.35, p<.001). Conclusion: Results indicate that to prevent the constantly increasing depression of middle-aged married couples, programs should be conducted for both of the couple, but focused differently for wife and husband.