Conductive adhesives have been used in a variety of electronic packaging applications. This paper presents an investigation into the effects of various adherend surface treatments on the fatigue and failure behaviors of adhesively-bonded joints. For this purpose, single-lap joints were fabricated using specimens with adherend surfaces modified employing various chemical and mechanical modification techniques, and tested under a spectrum of fatigue and environmental conditions. The results of our work indicate a profound influence of the adherend surface on both the fatigue behavior and also the moisture ingress mechanism into the joint. Finally, experiments were conducted to assess the effect of adherend surface condition on the moisture ingress mechanism.