Besides the well-known role of hormonal factors in mineral and bone metabolism, the sympathetic nervous system participates in this regulation by inhibiting bone formation and promoting bone resorption, primarily via β-adrenergic receptors expressed on osteoblasts. Conversely, the parasympathetic system, through cholinergic signalling, inhibits osteoclast activity, promoting bone formation and maintaining skeletal homeostasis. This review presents the role of the autonomic nervous system, with particular focus on the potential role of β-blockers, especially β1-selective blockers, in modulating bone health in people with normal kidney function and those with CKD. While early studies with non-selective β-blockers like propranolol showed mixed results, recent findings in postmenopausal women suggested that β1-selective β-blockers could enhance bone density by modulating sympathetic activity. Trial emulation using large databases and eventually randomized controlled trials are needed to test the hypothesis that β-blockade can favourably impact bone disease in patients with kidney failure.