Oral selective estrogen receptor degraders (SERDs) represent a novel endocrine therapy for estrogen receptor-positive (ER+) breast cancer. These drugs target and degrade the estrogen receptor (ER), reducing its activity and inhibiting the growth of ER+ breast cancer. Unlike first-generation SERDs like fulvestrant, which require intramuscular injection and have poor bioavailability, oral SERDs offer improved convenience and efficacy. Several oral SERDs are currently in clinical trials, with some, like elacestrant, already approved by the FDA for treating ER+ HER2-negative metastatic breast cancer with ESR1 mutations. Elacestrant, a nonsteroidal oral SERD, has shown promising results in clinical trials, including a 42.6% clinical benefit rate and a 33.3% objective response rate in patients with ESR1 mutations. It is well tolerated, with most adverse effects being mild to moderate. The EMERALD trial demonstrated that elacestrant improved progression-free survival compared to standard of care (SOC) endocrine therapy (fulvestrant or exemestane), particularly in patients with ESR1 mutations. Other oral SERDs under development include camizestrant, giredestrant, amcenestrant, imlunestrant, and rintodestrant. These drugs have shown varying degrees of efficacy and safety in clinical trials, with some demonstrating significant antitumor activity and manageable side effects. For example, camizestrant has shown a 28% clinical benefit rate in heavily pretreated patients, while giredestrant has demonstrated superior antiproliferation effects in early-stage ER+ breast cancer compared to aromatase inhibitors. Oral SERDs are being investigated in combination with CDK4/6 inhibitors and PI3K/AKT/mTOR-targeted therapies to enhance treatment efficacy and overcome resistance. Despite these advances, challenges remain in optimizing pharmacokinetics and understanding resistance mechanisms. Future research aims to address these issues and improve patient outcomes in ER+ breast cancer treatment. The development of oral SERDs represents a significant advancement in oncology, offering a more effective and less invasive treatment option for patients with ER+ breast cancer.Oral selective estrogen receptor degraders (SERDs) represent a novel endocrine therapy for estrogen receptor-positive (ER+) breast cancer. These drugs target and degrade the estrogen receptor (ER), reducing its activity and inhibiting the growth of ER+ breast cancer. Unlike first-generation SERDs like fulvestrant, which require intramuscular injection and have poor bioavailability, oral SERDs offer improved convenience and efficacy. Several oral SERDs are currently in clinical trials, with some, like elacestrant, already approved by the FDA for treating ER+ HER2-negative metastatic breast cancer with ESR1 mutations. Elacestrant, a nonsteroidal oral SERD, has shown promising results in clinical trials, including a 42.6% clinical benefit rate and a 33.3% objective response rate in patients with ESR1 mutations. It is well tolerated, with most adverse effects being mild to moderate. The EMERALD trial demonstrated that elacestrant improved progression-free survival compared to standard of care (SOC) endocrine therapy (fulvestrant or exemestane), particularly in patients with ESR1 mutations. Other oral SERDs under development include camizestrant, giredestrant, amcenestrant, imlunestrant, and rintodestrant. These drugs have shown varying degrees of efficacy and safety in clinical trials, with some demonstrating significant antitumor activity and manageable side effects. For example, camizestrant has shown a 28% clinical benefit rate in heavily pretreated patients, while giredestrant has demonstrated superior antiproliferation effects in early-stage ER+ breast cancer compared to aromatase inhibitors. Oral SERDs are being investigated in combination with CDK4/6 inhibitors and PI3K/AKT/mTOR-targeted therapies to enhance treatment efficacy and overcome resistance. Despite these advances, challenges remain in optimizing pharmacokinetics and understanding resistance mechanisms. Future research aims to address these issues and improve patient outcomes in ER+ breast cancer treatment. The development of oral SERDs represents a significant advancement in oncology, offering a more effective and less invasive treatment option for patients with ER+ breast cancer.