Pacific salmon migrations represent one of the most complex and intriguing biological phenomena in the animal kingdom particularly as the inability to reach spawning grounds results in zero lifetime fitness given their semelparous life history. In this presentation I review some key findings from our past 10 years of research involving the study of behavior, physiology and survival of up-river migrating adult sockeye salmon. Using physiological and conventional telemetry in field studies, and intervention experiments in laboratory flumes and tanks, we have discovered that when faced with challenging conditions towards the end of their migratory period (e.g. high or turbulent flows, high temperatures, confinement) females suffer 2-5X higher mortality than males. Such elevated mortality in females has been observed for sockeye passing through a fishway located within a short distance of spawning grounds. The causes of this phenomenon are still unclear though maturing female sockeye salmon maintain higher levels of circulating plasma cortisol compared to males, and we suspect that females could be immunocompromised and less resistant to pathogens whose rates of development are accelerated by stressful migratory conditions. The broader implications of this to fishway passage and reproductive success will be discussed.