The low-energy, long-lived isomer in 229Th, first studied in the 1970s as an exotic feature in nuclear physics, continues to inspire a multidisciplinary community of physicists. It has stimulated innovative ideas and studies that expand the understanding of atomic and nuclear structure of heavy elements and of the interaction of nuclei with bound electrons and coherent light. Using the nuclear resonance frequency, determined by the strong and electromagnetic interactions inside the nucleus, it is possible to build a highly precise nuclear clock that will be fundamentally different from all other atomic clocks based on resonant frequencies of the electron shell. The nuclear clock will open opportunities for highly sensitive tests of fundamental principles of physics, particularly in searches for violations of Einstein’s equivalence principle and for new particles and interactions beyond the standard model. It has been proposed to use the nuclear clock to search for variations of the electromagnetic and strong coupling constants and for dark matter searches. The 229Th nuclear optical clock still represents a major challenge in view of the tremendous gap of nearly 17 orders of magnitude between the present uncertainty in the nuclear transition frequency (about 0.2 eV, corresponding to ∼48 THz) and the natural linewidth (in the mHz range). Significant experimental progress has been achieved in recent years, which will be briefly reviewed. Moreover, a research strategy will be outlined to consolidate our present knowledge about essential 229mTh properties, to determine the nuclear transition frequency with laser spectroscopic precision, realize different types of nuclear clocks and apply them in precision frequency comparisons with optical atomic clocks to test fundamental physics. Two avenues will be discussed: laser-cooled trapped 229Th ions that allow experiments with complete control on the nucleus–electron interaction and minimal systematic frequency shifts, and Th-doped solids enabling experiments at high particle number and in different electronic environments.