diff --git a/gcloud/storage/blob.py b/gcloud/storage/blob.py
index 5190528115bb..a5e1201ee353 100644
--- a/gcloud/storage/blob.py
+++ b/gcloud/storage/blob.py
@@ -370,7 +370,8 @@ def upload_from_file(self, file_obj, rewind=False, size=None,
         :type size: int
         :param size: The number of bytes to read from the file handle.
                      If not provided, we'll try to guess the size using
-                     :func:`os.fstat`
+                     :func:`os.fstat`. (If the file handle is not from the
+                     filesystem this won't be possible.)
 
         :type content_type: string or ``NoneType``
         :param content_type: Optional type of content being uploaded.
@@ -382,6 +383,9 @@ def upload_from_file(self, file_obj, rewind=False, size=None,
                           ``NoneType``
         :param connection: Optional. The connection to use when sending
                            requests. If not provided, falls back to default.
+
+        :raises: :class:`ValueError` if size is not passed in and can not be
+                 determined
         """
         connection = _require_connection(connection)
         content_type = (content_type or self._properties.get('contentType') or
@@ -392,7 +396,13 @@ def upload_from_file(self, file_obj, rewind=False, size=None,
             file_obj.seek(0, os.SEEK_SET)
 
         # Get the basic stats about the file.
-        total_bytes = size or os.fstat(file_obj.fileno()).st_size
+        total_bytes = size
+        if total_bytes is None:
+            if hasattr(file_obj, 'fileno'):
+                total_bytes = os.fstat(file_obj.fileno()).st_size
+            else:
+                raise ValueError('total bytes could not be determined. Please '
+                                 'pass an explicit size.')
         headers = {
             'Accept': 'application/json',
             'Accept-Encoding': 'gzip, deflate',
diff --git a/gcloud/storage/test_blob.py b/gcloud/storage/test_blob.py
index 71b508870b4c..6203fb4be4b4 100644
--- a/gcloud/storage/test_blob.py
+++ b/gcloud/storage/test_blob.py
@@ -410,6 +410,16 @@ def test_download_as_string(self):
         fetched = blob.download_as_string(connection=connection)
         self.assertEqual(fetched, b'abcdef')
 
+    def test_upload_from_file_size_failure(self):
+        BLOB_NAME = 'blob-name'
+        bucket = _Bucket()
+        blob = self._makeOne(BLOB_NAME, bucket=bucket)
+        file_obj = object()
+        connection = _Connection()
+        with self.assertRaises(ValueError):
+            blob.upload_from_file(file_obj, size=None,
+                                  connection=connection)
+
     def _upload_from_file_simple_test_helper(self, properties=None,
                                              content_type_arg=None,
                                              expected_content_type=None):