Secondary lymphoid organs are important locations for the initiation of adaptive immune responses. They develop before birth, and their formation requires interaction between lymphotoxin-α₁β₂-expressing lymphoid-tissue inducer cells and lymphotoxin-β receptor-expressing stromal organizer cells. Here, we discuss new insights into the earliest phases of peripheral lymph node and Peyer's patch formation that occur before lymphotoxin-β receptor signalling and suggest a role for the developing nervous system. In addition, we discuss the differing requirements for the postnatal formation of mucosa-associated lymphoid tissues and tertiary lymphoid structures that develop at sites of chronic inflammation.