Current advances in human pluripotent stem cell (hPSC) technology allow directed differentiation into three-dimensional spinal organoid cultures that mimic the unique microenvironment and cytoarchitecture of the human spinal cord. Organoids also serves as important cellular tools to model spinal cord development and motor neuron diseases such as Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis. In this chapter, we describe a detailed step-by-step methodology to generate spinal organoids from human PSCs. We include advantages and limitations of the use of spinal organoids and notes on technical and design considerations in generating these spinal organoids.