This paper proposes a guidance scheme to operate ship defense missiles using dual seekersradio frequency and strapdown imaging infrared seekersagainst the threat of antiship missiles. Key challenges associated with considered operational concept such as the multipath error of an radio frequency seeker, the narrow field of view of an strapdown imaging infrared seeker, and the interference between the target and defense missiles are identified. A guidance scheme that can address these challenges is proposed by combining an optimal guidance law for the midcourse phase and the proportional navigation guidance for the terminal phase. A relationship among interceptor/target velocity, minimum line-of-sight angle for the radio frequency seeker, and the field of view of the strapdown imaging infrared seeker for a successful intercept is analytically derived and graphically presented. Numerical simulations for the engagements between ship defense missiles and an antiship missile demonstrate the validity of the proposed guidance scheme.