Patients with advanced prostate cancer (PCa) frequently develop skeletal metastases that are associated with fractures, disability, and increased mortality. Within the bone metastatic niche, mutual interactions between tumor cells and osteoblasts have been proposed as major contributors of osteotropism by PCa. Here, we highlight the emerging role of PCa-derived extracellular vesicles (EVs) in reprogramming osteoblasts and support of premetastatic niche formation. We also develop the concept of cancer-associated osteoblasts (CAOs) and outline the potential of PCa cells to acquire an osteoblastic phenotype, termed osteomimicry, as two strategies that PCa utilizes to create a favorable protected niche. Finally, we delineate future research that may help to deconstruct the complexity of PCa osteotropism.