The overall goal of this dissertation was to examine the musculotendinous adaptations in the lower leg and foot when habitually shod rearfoot-striking distance runners transitioned to true barefoot running. To achieve this, four studies were undertaken. The first study was to determine how novice barefoot runners respond to a bout of exertion (a dose of running), compared to the response to the same dose of exertion in the habitual shod condition. There were strong correlations between strike index and the exertion related i) decline in plantarflexor muscle peak torque and ii) peak rate of torque development; as well as with the iii) increased activation of the soleus during the early loading phase of stance. The soleus is preferentially activated during barefoot running, potentially leading to greater long term adaptations. Muscle performance, soleus activation and ankle joint coactivation also demonstrate significant changes in the novel barefoot rearfoot-strike condition, indicating that being barefoot alone causes changes in neuromuscular control. The purpose of the second study was to quantify plantarflexor musculotendinous unit adaptations to a nine-week transition to barefoot running in this cohort of shod runners. This prospective study demonstrated increases in plantarflexor muscle torque, as well as increases in pennation angle and volume of the soleus, in runners who adopted a forefootor midfoot-strike landing pattern. This is due to the greater relative loading of the soleus during the more flexed knee and more plantarflexed ankle during landing in barefoot running. The training effects of barefoot running are driven by running with a forefoot- or midfoot-strike landing pattern. Therefore runners who continue to rearfoot-strike in barefoot may not realize the hypertrophic effects on the plantarflexors, particularly the soleus. These hypertrophic adaptations are beneficial towards endurance related plantarflexor activity. In the third study, a Magnetic Resonance Imaging (MRI) based method of measuring intrinsic foot muscle volume was investigated in order to establish validity and reliability. This was achieved through a comparison with the gold standard - cadaver dissection volume. This study was necessary in order to reliably quantify long term intrinsic foot muscle adaptations in barefoot runners. The results showed excellent intra-rater validity and reliability for volume measurements of abductor hallucis, abductor digiti minimi, quadratus plantae, and flexor digitorum brevis. The purpose of the fourth study was to quantify foot muscle volume changes and foot bone stress in shod runners who completed a nine-week transition to true barefoot running. Significant increases of volume were noted in the abductor hallucis and quadratus plantae, driven by adoption of a forefoot- or midfoot-strike landing pattern. The ability to increase intrinsic foot muscle volume, and thereby strength, has clinical implications in the treatment of foot pathologies and in the prevention and rehabilitation of foot injuries in athletes. Rearfoot-strike runners demonstrated comparative increases in calcaneal water content, while midfoot and forefoot-strike runners had comparative increases in the first and second metatarsal bone water content. In each group, these bones may experience more stress injuries, compared to the other bones. The transition to barefoot running should be gradual, and should encourage forefoot-strike running in order realize the hypertrophic effects of barefoot running. Attention should also be paid to running on softer, natural surfaces. The training effects of barefoot running are relevant in the treatment of foot pathologies as well as in injury prevention, rehabilitation and performance enhancement in athletes.