With the increasingly early diagnosis of breast cancer and the advent of breast tumor subtyping, the need for determining which patients need adjuvant therapy has become more pressing and more complex. While clinical and pathologic features to predict benefit are valuable, the use of molecular techniques to better determine which tumors will benefit from chemotherapy is expected to further improve outcomes, reduce long-term complications, and provide cost-effective care. We will review the primary tools in clinical use: Adjuvant!, Oncotype DX, and MammaPrint as well as intrinsic subtypes and the plans for their further assessment in the clinical trial setting. The expected benefit from these models are that treatment recommendations for women with early-stage breast cancer will become more individualized and thereby appropriate by combining standard clinicopathologic and molecular features. This concept is currently being evaluated in multiple well-designed clinical trials.