The intimate admixing of bone matrix and bone marrow is a central point in devising therapy of metastatic lesions. Since specific modalities are not yet available for destroying the malignant cells, treatment is usually palliative. The use of stable gallium (Ga-nitrate) and of a diphosphonate (aminohydroxypropylidine diphosphonate disodium) as osteoclast inhibitors is discussed. The marrow, as well as the matrix, can be affected by external radiation. This is also true with bone-seeking radiopharmaceuticals. There is no ideal radiopharmaceutical available for treating metastases in bone, but the characteristics of several presently available (or proposed) are discussed, and possible use of tumor radiation sensitizers or bone marrow protectors is mentioned. Difficulties are also encountered in calculating accurate dosimetry. Clinical experience is needed to determine a reasonable optimal dose with any particular radiopharmaceutical for relief of pain with low bone marrow toxicity.