Prey organisms have developed a variety of physiological and behavioral strategies to avoid, or mitigate, predation. Some are capable of regenerating tissue after sublethal predation, the non-fatal removal and consumption of a body part; however, the events leading up to arm loss in cryptic organisms such as octopuses are poorly understood. Octopuses have eight multifunctional, regenerative arms used to explore, handle objects, and presumably, defend against predators. In this dissertation, I explored the patterns of arm loss experienced by octopuses across species and ontogeny, as well as behaviors that put these arms at the highest risk. In Chapter 1, I observed injured arms, calculating scaling relationships specific to the arms of three sympatric Octopus species to calculate the proportion of arm truncation. Arm injuries in these species were frequent and asymmetrical, and that when injured, octopus on average lost about one-third of an arm. These injuries were biased to the anterior left arms, L1 and L2. However, different measures of injury supported very different conclusions. Therefore, in Chapter 2, I created and demonstrated the utility of an Injury Severity Index (ISI) to describe the magnitude of appendage injury in invertebrates, using counts and proportions of arm losses collected from octopuses in museums and the field. Museum specimens had most commonly lost part of one arm, with a mode ISI value of less than 2.00. Wild O. bimaculatus had a mean ISI value of 3.13, representing two to three arm injuries. I also calculated volume of lost tissue based on the shape of a cone to further enhance quantifications of arm loss. In Chapter 3, I describe the ways in which O. bimaculatus used their arms in self-defense against a common predator (Gymnothorax mordax). Octopuses and morays were observed interacting freely in tanks. Suites of antipredator strategies varied greatly by sex, leading to greater success for males avoiding an attack. Individual arm use was biased toward arm L1 and neighboring arms, and predatory bites were concentrated on L2 and its neighbors. This dissertation revealed octopus arm use and loss from high-risk contexts, with a bias toward anterior-left arms across species.